Synthesis of 6-O-hexadecyl-and 6-O-octylsucroses and their self-assembling properties under aqueous conditions

Article abstract of DOI:10.1080/07328303.2012.702250

This paper reports the synthesis and self-assembling properties of 6-O-hexadecyl-and 6-O-octylsucroses. Mono-etherification of 2,3,4,1,3,4-hexa-O- benzylsucrose with the corresponding alkyl bromides predominantly took place at the glucose 6-position and t

Full text of DOI:10.1080/07328303.2012.702250

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Synthesis of 6-O-Hexadecyl- and 6-O-
Octylsucroses and Their Self-Assembling
Properties Under Aqueous Conditions
Sachie Ohkawabata a , Manami Kanemaru a , Shin-ya Kuawahara a ,
Kazuya Yamamoto a & Jun-ichi Kadokawa a
a Department of Chemistry, Biotechnology, and Chemical
Engineering, Graduate School of Science and Engineering,
Kagoshima University, Kagoshima, 890-0065, Japan
Version of record first published: 31 Oct 2012.
To cite this article: Sachie Ohkawabata, Manami Kanemaru, Shin-ya Kuawahara, Kazuya Yamamoto
& Jun-ichi Kadokawa (2012): Synthesis of 6-O-Hexadecyl- and 6-O-Octylsucroses and Their Self-
Assembling Properties Under Aqueous Conditions, Journal of Carbohydrate Chemistry, 31:8, 659-672
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Journal of Carbohydrate Chemistry, 31:659–672, 2012
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Copyright Taylor & Francis Group, LLC
ISSN: 0732-8303 print / 1532-2327 online
DOI: 10.1080/07328303.2012.702250
Synthesis of 6-O-Hexadecyl-
and 6-O-Octylsucroses and
Their Self-Assembling
Properties Under Aqueous
Conditions
Sachie Ohkawabata, Manami Kanemaru,
Shin-ya Kuawahara, Kazuya Yamamoto,
and Jun-ichi Kadokawa
Department of Chemistry, Biotechnology, and Chemical Engineering, Graduate School
of Science and Engineering, Kagoshima University, Kagoshima 890-0065, Japan
This paper reports the synthesis and self-assembling properties of 6-O-hexadecyl- and
6-O-octylsucroses. Mono-etherification of 2,3,4,1ꢁ,3ꢁ,4ꢁ-hexa-O-benzylsucrose with the
corresponding alkyl bromides predominantly took place at the glucose 6-position and
the products were isolated by silica gel column chromatography. Benzyl groups in the
isolated products were cleaved to yield the target derivatives. The SEM, TEM, XRD,
and DLS results indicated that 6-O-alkylsucroses formed vesicle-type particles via for-
mation of lamellar-like planes under aqueous conditions, which were further merged
by fusion of the planes to construct larger aggregates. The self-assembling properties
of the materials were different from those of the previously reported 6-O- and 6’-O-
hexadecylsucroses mixture.
Keywords Sucrose; Monoalkyl ether; Self-assembly; Vesicle; Lamellar
INTRODUCTION
Amphiphilic molecules, of which soap is a typical example, possess antago-
nistic hydrophilic and hydrophobic moieties in the same molecule. In aque-
ous media, such molecules self-assemble into various controlled morphologies,
Received April 16, 2012; accepted June 8, 2012.
Address correspondence to Jun-ichi Kadokawa, Department of Chemistry, Biotech-
nology, and Chemical Engineering, Graduate School of Science and Engineer-
ing, Kagoshima University, 1-21-40 Korimoto, Kagoshima 890-0065, Japan. E-mail:
kadokawa@eng.kagoshima-u.ac.jp
659

S. Ohkawabata et al.
660
such as spherical micelles, cylindrical micelles, spherical vesicles, planar bi-
layers, and tubes, depending on the molecular shape and solution conditions.[1]
Because glycolipids, which are natural amphiphiles containing carbohydrates
as a hydrophilic part, exhibit important in vivo functions in living systems,[2]
synthetic carbohydrate-based amphiphiles have been previously studied ex-
tensively to show a large variety of self-assembling morphologies.[1]
On the other hand, the synthetic carbohydrate-based amphiphiles have
been used as an emulsifier in various food industries.[3] One of the most ef-
fective food additives, practically employed, is the sucrose fatty acid ester,
which contains a sucrose residue as a hydrophilic part and a long-alkyl fatty
acid moiety as a hydrophobic part.[4] Self-assembling properties of the sucrose
fatty acid esters are changed depending on the lengths and types of fatty
acid chains.[5] Compared with such sucrose ester amphiphiles, self-assembling
studies using sucrose-based amphiphiles connecting with long-alkyl chains
by ether linkages (i.e., sucrose alkyl ethers) have been less reported. As one
of the examples, the effect of molecular shape on the liquid crystal properties
of mono-O-(2-hydroxydodecyl)sucroses, which were prepared by the reaction
of sucrose with 1,2-epoxydodecane under alkaline conditions, was reported.[6]
On the basis of the above viewpoint, in the previous paper, we reported the
self-assembling property of a mixture of 6-O- and 6’-O-hexadecylsucroses (6-
mono-C16 and 6ꢁ-mono-C16, respectively) under aqueous conditions, which
were new sucrose-based amphiphiles having the structures of a sucrose residue
connecting with a hexadecyl chain by the ether linkage at the 6- or 6ꢁ-
position.[7] From the analytical results, the following self-assembling process of
such mono-O-alkylsucrose mixtures under aqueous conditions was proposed.
The mixture primarily formed spherical micelles with diameters of ca. 5 to
7 nm in water. The micelles regularly organized according to face-centered
cubic (FCC) structure during the drying process from the aqueous disper-
sion to construct nanoparticles with diameters of ca. 50 nm. Moreover, sev-
eral numbers of the nanoparticles further assembled to form larger aggre-
gates. However, the more precise study on the self-assembling properties of
the individual 6-mono-C16 and 6ꢁ-mono-C16 under aqueous conditions has
not been achieved because these two isomers could not be separated from
the mixture by general experimental techniques such as column chromatog-
raphy.
To investigate the detailed self-assembling property of such mono-O-
alkylsucroses, in the continuous study, we have attempted synthesis of a sole
6-mono-C16 from sucrose. Consequently, in this paper, we report that mono-
etherification of 2,3,4,1ꢁ,3ꢁ,4ꢁ-hexa-O-benzylsucrose (3), which had two free hy-
droxy groups at the 6- and 6ꢁ-positions, predominantly took place at the glucose
6-position by the reaction with 1-bromohexadecane under selected conditions
(Sch. 1). A major product (4a) by the etherification at the 6-position, moreover,
could be separated from a minor product yielded by the etherification at the

Synthesis of 6-O-Hexadecyl- and 6-O-Octylsucroses
661
Scheme 1: Synthesis of 6-O-hexadecylsucrose (6-mono-C16) and 6-O-octylsucrose
(6-mono-C8) from sucrose.
6ꢁ-position by the simple silica gel column chromatographic technique. Thus,
the following debenzylation of the isolated product gave a pure 6-mono-C16.
Self-assembling property of the obtained 6-mono-C16 was evaluated accord-
ing to the similar experimental manners as those of the previously reported
6-mono-C16 and 6ꢁ-mono-C16 mixture using the SEM, TEM, powder X-
ray diffraction (XRD), and dynamic light scattering (DLS) measurements.[7]
Consequently, it was found that 6-mono-C16 showed a hierarchically self-
assembling process based on the primary formation of lamellar planes, leading
to vesicle-type particles. The particles further assembled to construct larger ag-
gregates probably by fusion of the planes between the particles. These results
indicated that the self-assembling process of the sole 6-mono-C16 molecule
was completely different from that of its mixture with the regioisomer, 6ꢁ-
mono-C16, which took place based on the primary formation of the spheri-
cal micelles. It is also reported in this paper that other 6-O-alkylsucrose with
a different chain length, that is, 6-O-octylsucrose (6-mono-C8), was also syn-
thesized from sucrose according to the same procedure, and its self-assembling
process was found to be similar to that of 6-mono-C16.
RESULTS AND DISCUSSION
We first attempted synthesis of 6-mono-C16 via mono-tritylation, followed
by the appropriate reactions because the isolation of 6-O-tritylsucrose from
the products containing 6ꢁ-O-tritylsucrose by mono-tritylation of sucrose was

S. Ohkawabata et al.
662
already reported.[8] However, the complete separation according to such
literature procedure was not achieved well by us at present. As the alterna-
tive approach to that via mono-tritylation, therefore, we selected the procedure
through di-tritylation, followed by benzylation, detritylation, etherification,
and debenzylation. During the present approach, we found that mono-
etherification of 2,3,4,1ꢁ,3ꢁ,4ꢁ-hexa-O-benzylsucrose (3) having two free hydroxy
groups at the 6- and 6ꢁ-positions, which was prepared by di-tritylation of
sucrose, followed by benzylation and detritylation, with 1-bromohexadecane
predominantly took place at the glucose 6-position under selected conditions
because of the higher reactivity of the 6-hydroxy group than the 6ꢁ-hydroxy
group. Furthermore, it was also found that 6-hexadecylated derivative 4a as
a major product could be separated from 6ꢁ-hexadecylated derivative as a mi-
nor product by simple silica gel column chromatography owing to relatively
different values in rates of flow (Rf) of the two materials eluted with ethyl ac-
etate:hexane = 1:50 (v/v) on silica gel. This fact was much different from that
which appeared in other 6- and 6ꢁ-regioisomers of sucrose such as 6-mono-C16
and 6ꢁ-mono-C16 because such regioisomers generally eluted at the almost
same Rf value on silica gel.
Accordingly, the synthesis of 6-mono-C16 was carried out by five reaction
steps from sucrose according to Scheme 1, which were successive di-tritylation
at the 6- and 6ꢁ-posititons, benzylation of other free hydroxy groups, detrity-
lation, etherification at the 6-posititon, and debenzylation.[9–11] Although the
first tritylation selectively took place at the primary hydroxy groups, three
kinds of the tritylated products (i.e., mono-, di-, and tri-O-tritylsucroses) were
formed. Therefore, a target molecule of 6,6ꢁ-di-tritylated sucrose 1 was sepa-
rated from the crude products by silica gel column chromatography, and ac-
cordingly the isolated yield was not high (27.4%). It was confirmed further by
its acetylation experiment using acetic anhydride and pyridine that the trityl
groups were present at the 6- and 6ꢁ-positions, but not at the 1ꢁ-position of the
other primary hydroxy group in the isolated compound. The 1H NMR spectrum
(CDCl3) of the acetylated derivative showed that chemical shifts of the signals
assignable to the H-6 and H-6ꢁ protons were not changed compared with those
before the acetylation, whereas the signals due to the protons at other positions
(besides H-1) were shifted to the lower magnetic field. These data indicated
that the 6- and 6ꢁ-positions were tritylated in the aforementioned product and,
accordingly, were not acetylated by acetic anhydride.
The following benzylation smoothly proceeded and the product 2 was iso-
lated in a relatively high yield (87.3%) by recrystallization. Because a gly-
cosidic linkage in the sucrose derivatives was weak under the acidic condi-
tions,[11] detritylation of the product was carefully performed under the mild
conditions, but the yield of 3 was not high (31.6%). The subsequent etherifi-
cation using an equivalent of 1-bromohexadecane for 3 with sodium hydride
at rt for 1 h predominantly took place at the 6-position. The product 4a was

Synthesis of 6-O-Hexadecyl- and 6-O-Octylsucroses
663
separated from the 6ꢁ-etherified product by silica gel chromatography, although
the isolated yield was low (8.0%). Then, debenzylation of the product was con-
ducted by catalytic hydrogenation to give 6-mono-C16.
1
The structure of 6-mono-C16 was determined by the H NMR analysis
in CD3OD as shown in Figure 1a. The signals’ assignments are as follows: δ
0.82 (t, 3H, CH3, J = 6.8 Hz), 1.03–1.19 (m, 26H, -(CH2)13-CH3), 1.50–1.54 (m,
2H, -O-CH2-CH2-), 3.21–4.00 (m, 15H, H-1’,2,3,3ꢁ,4,4ꢁ,5,5ꢁ,6,6ꢁ, -O-CH2-CH2-),
5.27 (d, 1H, H-1, J = 3.6 Hz). The mono-etherified structure was confirmed by
the integrated ratio of the signals due to CH3 of the hexadecyl group to the
signal due to an H-1 proton of the glucose residue, which was 3:1. The MALDI-
TOF MS showed a significant peak corresponding to the molecular mass of
[6-mono-C16]Na+ (found; m/z 589.4320, calcd; m/z 589.3564). The structure
of the product was confirmed further by its acetylation experiment using acetic
Figure 1: 1H NMR spectra of (a) 6-mono-C16 (CD3OD) and (b) its acetylated derivative
(CDCl3).

S. Ohkawabata et al.
664
anhydride and pyridine. The 1H NMR spectrum in CDCl3 (Fig. 1b) of the acety-
lated derivative showed that chemical shift of the signals assignable to the
H-6 protons was not changed compared with that before acetylation (Fig. 1a),
whereas the signals due to other positions including the H-6ꢁ position were
shifted to the lower magnetic field. This data indicated that only the 6-position
was etherified in the aforementioned product and, accordingly, was not acety-
lated by acetic anhydride. All the above analytical and acetylation results can
be taken to support the structure of 6-mono-C16.
The other derivative, 6-O-octylsucrose (6-mono-C8), was also synthesized
by the same manner as previously mentioned. The structure of the product was
1
confirmed by the H NMR spectrum and MALDI-TOF MS (see Experimental
section). Then, two derivatives, 6-mono-C16 and 6-mono-C8, were subjected
to the following self-assembling investigations under aqueous conditions.
In the SEM image (Fig. 2a) of a sample of 6-mono-C16 on an aluminum
plate, which was prepared by drying its dispersion in water (1.0 × 10−5 mol/L),
particle-type nanoaggregates with an average diameter of ca. 51 nm were seen.
Although this value was similar to that observed in the previously reported
SEM image of a sample of the 6-mono-C16 and 6ꢁ-mono-C16 mixture pre-
pared by the same procedure, the standard deviation in the diameters of the
present particles was much larger than that in the diameters of the particles
from the mixture (12.8 and 4.34, respectively). The SEM image in Figure 2a,
Figure 2: SEM images of the samples prepared from dispersions of (a) 6-mono-C16 and (b)
6-mono-C8; TEM images of the samples prepared from dispersions of (c) 6-mono-C16 and
(d) 6-mono-C8 in water (1.0 × 10−5 mol/L); and (e) a magnified TEM image of (d).

Synthesis of 6-O-Hexadecyl- and 6-O-Octylsucroses
665
furthermore, did not show larger aggregates by further assembly from the sev-
eral particles as observed in that of the mixture. The TEM image (Fig. 2c) of
a sample of 6-mono-C16 prepared from its dispersion in water (1.0 × 10−5
mol/L) exhibited vesicle-like particles, which further assembled to form larger
aggregates, whereas such vesicle morphology in the particles was not seen in
the TEM image of a sample of the 6-mono-C16 and 6ꢁ-mono-C16 mixture (im-
age not shown). These results suggested that the self-assembling process of a
sole 6-mono-C16 under aqueous conditions was probably different from that
of the 6-mono-C16 and 6ꢁ-mono-C16 mixture under the same conditions.
The SEM image (Fig. 2b) of a sample of 6-mono-C8 on an aluminum plate
prepared by the same procedure as above also showed particle-type nanoaggre-
gates, but their average diameter (ca. 117 nm) was larger than that in Figure
2a (the standard deviation, 14.4). The TEM image (Fig. 2d) of a sample of 6-
mono-C8 also showed vesicles and their assemblies as observed in Figure 2c.
Furthermore, the image showed that the vesicle was constructed from lamel-
lar planes of 10-odd alternating black and white layers, where the former and
latter probably corresponded to the self-organized hydrophilic sucrose and hy-
drophobic octyl layers, respectively. Interestingly, the lamellar planes at the
interfacial area between the two vesicles were merged as observed in the mag-
nified TEM image (Fig. 2e).
To confirm the self-assembling processes of the present materials further,
the XRD and DLS measurements were conducted. In the XRD profiles (Fig. 3)
of the samples, which were prepared by drying aqueous dispersions of 6-mono-
C16 and 6-mono-C8 (1.0 × 10−3 mol/L), diffraction peaks due to (001) (Figs.
3a and 3b) and further peaks assignable to the (002), (003), and (004) Bragg re-
flections (Fig. 3a) of lamellar patterns were observed. From the XRD patterns,
widths of the lamellar layers were calculated to be 3.9 nm for 6-mono-C16 and
2.9 nm for 6-mono-C8 as decreased with decreasing the alkyl chain lengths.
Both the DLS results (Fig. 4) of dispersions of 6-mono-C16 and 6-mono-C8
in water (1.0 × 10−5 mol/L) showed monomodal profiles with relatively narrow
distributions. An average diameter of the former (99.8 nm) was smaller than
that of the latter (105.7 nm), and thus, the tendency was similar to that which
appeared in the SEM measurement. The difference in the average diameters
by the DLS and SEM measurements was probably because of the different
calculation methods for the average diameters in both the measurements, in
which the average diameter in the DLS measurement was calculated from the
intensity of scattering light, which was proportional to d6 (d: diameter of a
particle), whereas number distribution was used for calculation of the average
diameter of particles in the SEM measurement.[12] Furthermore, the wet and
dry sample conditions in the two measurements probably affected the differ-
ence in the particle sizes. The XRD and DLS results of the 6-mono-C16 and
6ꢁ-mono-C16 mixture measured under the same conditions were completely

S. Ohkawabata et al.
666
Figure 3: XRD profiles of the samples prepared from dispersions of (a) 6-mono-C16 and (b)
6-mono-C8 in water (1.0 × 10−3 mol/L).
different from the present results. The XRD profile of the mixture showed the
pattern assignable to the FCC organization, and an average diameter of the
particles in the DLS measurement of the mixture in water was 7.1 nm, corre-
sponding to a diameter of the spherical micelle.[7]
The above analytical results indicated that both of the self-assembling pro-
cesses of 6-mono-C16 and 6-mono-C8 under aqueous conditions equally took
place, in which the vesicle-like particles were primarily obtained on the basis
of lamellar planes, which were constructed by the self-organized alternating
hydrophilic sucrose and hydrophobic alkyl layers. Some of the vesicles were
merged further by fusion of the planes at the interfacial area (Fig. 5). Thus,
the particles observed in the SEM images and the DLS profiles probably corre-
sponded to a sole vesicle or the merged vesicles. As we previously reported,[7]
however, the self-assembly of the 6-mono-C16 and 6ꢁ-mono-C16 mixture did
not induce the formation of a vesicle-like particle, but led to the spherical mi-
celle in water, which was separately present in aqueous dispersion as indicated
by the DLS measurement. The spherical micelles assembled further according

Synthesis of 6-O-Hexadecyl- and 6-O-Octylsucroses
667
Figure 4: DLS profiles of (a) 6-mono-C16 and (b) 6-mono-C8 in water (1.0 × 10−5 mol/L).
to the FCC organization by drying the aqueous dispersion to construct the
nanoparticles and larger aggregates by their assembly. The reason for the dif-
ference in the self-assembling processes of the sole 6-mono-C16 (or 6-mono-
C-8) and the 6-mono-C16 and 6ꢁ-mono-C16 mixture is not yet clear, but it is
assumed that a couple of regioisomers, 6-mono-C16 and 6ꢁ-mono-C16, con-
struct the favorable structure to assemble the spherical micelle.
Figure 5: Plausible self-assembling processes of 6-mono-C16 and 6-mono-C8 under aqueous
conditions.

S. Ohkawabata et al.
668
CONCLUSION
This study investigated the synthesis of 6-mono-C16 and 6-mono-C8 through
mono-etherification of a sucrose derivative having two free hydroxy groups at
the 6- and 6ꢁ-positions with the corresponding alkyl bromides under selected
conditions. The mono-etherification at the glucose 6-position predominantly
took place against that at the 6ꢁ-position and the 6-monoether derivative as
a major product was separated from the 6ꢁ-monoether derivative as a minor
product by silica gel column chromatography. The structures of the products
were established by the 1H NMR and MALDI-TOF MS measurements as well
as the acetylation experiment. The self-assembling properties of these mate-
rials under aqueous conditions were evaluated by the SEM, TEM, XRD, and
DLS measurements. They primarily formed the vesicle-type particles via the
formation of lamellar-like planes in water, and some of which merged further
because of fusion of the planes at the interfacial area between the vesicles. The
self-assembling processes of the present materials were completely different
from those of the 6-mono-C16 and 6ꢁ-mono-C16 mixture reported in our pre-
vious paper, which progressed via the FCC organization of the primary formed
spherical micelles. The detailed study to reveal the reason for the difference in
the self-assembling properties of a sole 6-O-alkylsucrose and its mixture with
the regioisomer, 6ꢁ-O-alkylsucrose is now in progress in our group and will be
published in a forthcoming paper.
EXPERIMENTAL
General
All reagents were available commercially and used without further pu-
rification. DMF was purified by distillation over calcium hydride. Other sol-
vents were used as received. 1H NMR spectra were recorded on a JEOL
ECX400 spectrometer. MALDI-TOF MS measurements were carried out by
using SHIMADZU Voyager Biospectrometry Workstation Ver .5.1 with 2.5-
dihydroxybenzoic acid as matrix containing 0.05% trifluoroacetic acid under
positive ion mode. SEM images were obtained using a Hitachi S-4100H elec-
tron microscope. TEM measurements were operated using Jeol JEM-3010 un-
der 200 kV. XRD measurements were conducted using a PANalytical X’Pert
Pro MPD with Ni-filtered CuKα radiation (λ = 0.15418 nm). DLS measure-
ments were performed on a Zetasizer Nano ZS (Malvern Instruments).
Synthesis of 6-O-Hexadecylsucrose
Under argon, to a dispersion of sucrose (3.42 g, 10.0 mmol) in pyri-
dine (20.0 mL) was added a solution of triphenylmethyl chloride (5.57 g,

Synthesis of 6-O-Hexadecyl- and 6-O-Octylsucroses
669
20.0 mmol) in pyridine (10.0 mL) at rt, and the mixture was stirred
for 72 h at that temperature. After the reaction mixture was concen-
trated and diluted with chloroform, the solution was successively washed
with 10% KHSO4 aq. and water, dried over anhydrous Na2SO4, filtered,
and evaporated. The residue was subjected to column chromatography on
silica gel (eluent; chloroform:methanol = 22:1 (v/v)) to give 1 (2.27 g,
2.74 mmol) in 27.4% yield. 1H NMR (CD3OD): δ 3.14–4.20 (m, 13H, H-
1ꢁ,2,3,3ꢁ,4,4ꢁ,5,5ꢁ,6,6ꢁ), 5.47 (d, 1H, H-1, J = 2.2 Hz), 7.13–7.20 (m, 30H,
aromatics).
Under argon, to a dispersion of NaH (4.92 g, 82.1 mmol) in DMF (76.0 mL)
was added a solution of 1 (4.54 g, 5.47 mmol) in DMF (61.0 mL) at rt, and
the mixture was stirred at that temperature for 30 min. After a solution of
tetrabutylammonium bromide (small amount) in DMF and benzyl bromide
(5.90 mL, 49.2 mmol) were added to the mixture, the reaction was conducted
at rt for 48 h. The reaction was stopped by addition of methanol to the reaction
mixture. After the resulting mixture was concentrated and diluted with chlo-
roform, the solution was washed with water, dried over anhydrous Na2SO4, fil-
tered, and evaporated. The residue was recrystallized from methanol/acetone
1
(20:1 (v/v)) to give 2 (6.54 g, 4.77 mmol) in 87.3% yield. H NMR (CDCl3): δ
2.89–4.04 (m, 13H, H-1ꢁ,2,3,3ꢁ,4,4ꢁ,5,5ꢁ,6,6ꢁ), 4.18–4.81 (m, 12H, CH2-Ph), 6.34
(d, 1H, H-1, J = 4.0 Hz), 7.05–7.53 (m, 60H, aromatics).
To a solution of 2 (0.778 g, 0.638 mmol) in ice-cold dichloromethane-acetic
acid (4.5 mL, 2 : 1 (v/v)) was added dropwise a small amount of conc. HCl.
After the reaction was carried out at the ice-cold temperature for 3.5 h, the re-
action mixture was diluted with dichloromethane, neutralized with saturated
NaHCO3 aq., washed with water, dried over anhydrous Na2SO4, filtered, and
evaporated. The residue was subjected to column chromatography on silica gel
(eluent; ethyl acetate:hexane = 1:6 (v/v)) to give 3 (0.178 g, 0.202 mmol) in
1
31.6% yield. H NMR (CDCl3): δ 3.41–4.15 (m, 13H, H-1ꢁ,2,3,3ꢁ,4,4ꢁ,5,5ꢁ,6,6ꢁ),
4.29–4.81 (m, 12H, CH2-Ph), 5.49 (d, 1H, H-1, J = 3.6 Hz), 7.21–7.33 (m, 30H,
aromatics).
Under argon, to a dispersion of NaH (0.0069 g, 0.11 mmol) in DMF (1.0 mL)
was added a solution of 3 (0.099 g, 0.11 mmol) in DMF (2.0 mL) at rt and the
mixture was stirred at that temperature for 30 min. After a solution of tetra-
butylammonium bromide (small amount) in DMF and 1-bromohexadecane
(0.034 mL, 0.11 mmol) were added to the mixture, the reaction was con-
ducted at rt for 1 h. The reaction was stopped by addition of methanol to the
reaction mixture. After the resulting mixture was concentrated and diluted
with chloroform, the solution was washed with water, dried over anhydrous
Na2SO4, filtered, and evaporated. The residue was subjected to chromatogra-
phy on silica gel (eluent; ethyl acetate:hexane = 1:50 (v/v)) to give 4a (0.0097 g,
0.0088 mmol) in 8.0% yield. 1H NMR (CDCl3): δ 0.88 (t, 3H, CH3, J = 7.0 Hz),
1.23–1.25 (m, 26H, -(CH2)13-CH3), 1.56–1.70 (m, 2H, -O-CH2-CH2-), 3.25–4.08

S. Ohkawabata et al.
670
(m, 15H, H-1ꢁ,2,3,3ꢁ,4,4ꢁ,5,5ꢁ,6,6ꢁ, -O-CH2-CH2-), 4.24–4.88 (m, 12H, CH2-Ph),
5.52 (d, 1H, H-1, J = 3.2 Hz), 7.19–7.34 (m, 30H, aromatics).
To a solution of 4a (0.020 g, 0.018 mmol) in a mixed solvent of butanol
(6.4 mL), methanol (0.64 mL), and water (0.16 mL) was added 10% palla-
dium on carbon (0.0051 g) and the mixture was stirred at rt for 8 days un-
der hydrogen atmosphere. After the reaction mixture was filtered and the fil-
trate was evaporated, the residue was subjected to column chromatography on
silica gel (eluent; chloroform:methanol = 10:1) to give 6-O-hexadecylsucrose
1
(6-mono-C16, 1, 0.0010 g, 0.018 mmol) in 99.0% yield. H NMR (CD3OD): δ
0.82 (t, 3H, CH3, J = 6.8 Hz), 1.03–1.19 (m, 26H, -(CH2)13-CH3), 1.50–1.54
(m, 2H, -O-CH2-CH2-), 3.21–4.00 (m, 15H, H-1ꢁ,2,3,3ꢁ,4,4ꢁ,5,5ꢁ,6,6ꢁ, -O-CH2-
CH2-), 5.27 (d, 1H, H-1, J = 3.6 Hz). MALDI-TOF MS: Calcd [C28H54O11]Na+:
m/z 589.3564. Found: m/z 589.4320.
Synthesis of 6-O-Octylsucrose
In the same way as 4a, 4b was prepared by the reaction of 3 with 3 equiv-
1
alents of 1-bromooctane at 80◦C for 2 days in 7.2% yield. H NMR (CDCl3):
δ 0.87 (t, 3H, CH3, J = 8.2 Hz), 1.23–1.27 (m, 10H, -(CH2)5-CH3), 1.56–1.70
(m, 2H, -O-CH2-CH2-), 3.25–4.08 (m, 15H, H-1ꢁ,2,2ꢁ,3,3ꢁ,4,4ꢁ,5,5ꢁ,6,6ꢁ, -O-CH2-
CH2-), 4.27–4.88 (m, 12H, CH2-Ph), 5.52 (d, 1H, H-1, J = 3.2 Hz), 7.21–7.32
(m, 30H, aromatics).
Then, synthesis of 6-O-octylsucrose (6-mono-C8) was carried out in the
1
same way as 6-mono-C16 from 4b in 45.0% yield. H NMR (CD3OD): δ 0.80
(t, 3H, CH3, J = 6.8 Hz), 1.28–1.29 (m, 10H, -(CH2)5-CH3), 1.50–1.56
(m, 2H, -O-CH2-CH2-), 3.20–4.25 (m, 15H, H-1’,2,3,3’,4,4’,5,5’,6,6ꢁ, -O-CH2-
CH2-), 5.36 (d, 1H, H-1, J = 3.6 Hz). MALDI-TOF MS: Calcd [C20H38O11]Na+:
m/z 477.2312. Found: m/z 477.3399.
Acetylation of 6-Mono-C16
A typical example is as follows. Under argon, a mixture of 6-mono-C16
(0.0041 g, 0.0072 mmol), acetic anhydride (0.15 mL), and pyridine (0.15 mL)
was stirred at rt for 24 h. The reaction mixture was poured into a large amount
of water to precipitate the product. The precipitate was dried under reduced
pressure to give the acetylated product (0.0050 g, 0.0058 mmol) in 80.0% yield.
1H NMR (CDCl3): δ 0.88 (t, 3H, -CH2-CH3, J = 6.8 Hz), 1.28–1.29 (m, 26H, -
(CH2)13-CH3), 1.57–1.60 (m, 2H, -O-CH2-CH2-), 2.02–2.18 (7s, 21H, O C-CH3),
3.36–3.55 (m, 4H, H-6, -O-CH2-CH2-), 4.13–4.33 (m, 6H, H-1ꢁ5,5ꢁ,6ꢁ), 4.86 (dd,
1H, H-2, J = 5.4, 1.8 Hz), 5.15 (t, 2H, H-4,4ꢁ, J = 9.8 Hz), 5.15–5.46 (m, 2H,
H-3,3’), 5.70 (d, 1H, H-1, J = 3.6 Hz).

Synthesis of 6-O-Hexadecyl- and 6-O-Octylsucroses
671
Preparation of Samples for SEM Measurement
A dispersion of 6-mono-C16 or 6-mono-C8 (1.0 × 10−5 mol/L) was placed
on an aluminum plate and it was left standing under ambient atmosphere
until water was evaporated. Then, the resulting solid sample was subjected to
the measurement.
Preparation of Samples for TEM Measurement
A dispersion of 6-mono-C16 or 6-mono-C8 (1.0 × 10−5 mol/L) was placed
on carbon film-coated copper grids. The negative-staining technique was used
for TEM sample preparation. Then, the preparative material was left standing
under ambient atmosphere until water was evaporated. Then, the resulting
solid sample was subjected to the measurement.
REFERENCES
1. (a) Shimizu, T. Bottom-up synthesis and structural properties of self-assembled
high-axial-ratio nanostructures. Macromol. Rapid Commun. 2002, 23, 311–331.
(b) Fuhrhop, J. -H.; Wang, T. Bolaamphiphiles. Chem. Rev. 2004, 104, 2901–2937.
(c) Shimizu, T.; Masuda, M.; Minakawa, H. Supramolecular nanotube architectures
based on amphiphilic molecules. Chem. Rev. 2005, 105, 1401–1443.
2. (a) Corti, M.; Cantu`, L.; Brocca, P.; Favero, E. D. Self-assembly in glycolipids. Curr.
Opin. Colloid Interface Sci. 2007, 12, 148–154. (b) Kitamoto, D.; Morita, T.; Fukuoka, T.;
Konishi, M.; Imura, T. Self-assembling properties of glycolipid biosurfactants and their
potential applications. Curr. Opin. Colloid Interface Sci. 2009, 14, 315–328.
3. Kralova, I.; Sjoblom, J. Surfactants used in food industry: a review. J. Dispersion
Sci. Technol. 2009, 30, 1363–1383.
4. (a) Hodate, Y.; Ueno, S.; Yano, J.; Katsuragi, T.; Tezuka, Y.; Tagawa, T.; Yoshimoto,
N.; Sato, K. Ultrasonic velocity measurement of crystallization rates of palm oil in oil-
water emulsions. Colloids Surf. A 1997, 128, 217–224. (b) Awad, T.; Sato, K. Effects
of hydrophobic emulsifier additives on crystallization behavior of palm mid fraction
in oil-in-water emulsion. J. Am. Oil Chem. Soc. 2001, 78, 837–842. (c) Katsuragi, T.;
Kaneko, N.; Sato, K. Effects of addition of hydrophobic sucrose fatty acid oligoesters on
crystallization rates of n-hexadecane in oil-in-water emulsions. Colloids Surf. B 2001,
20, 229–237. (d) Awad, T.; Sato, K. Acceleration of crystallisation of palm kernel oil in
oil-in-water emulsion by hydrophobic emulsifier additives. Colloids Surf. B 2002, 25,
45–53.
5. (a) Molinier, V.; Kouwer, P. J. J.; Fitremann, J.; Bouchu, A.; Mackenzie, G.; Que-
neau, Y.; Goodby, J. W. Chem. Eur. J. 2006, 12, 3547–3557. (b) Goodby, J. W.; Go¨rtz, V.;
Cowling, S. J.; Mackenzie, G.; Martin, P.; Plusquellec, D.; Benvegnu, T.; Boullanger,
P.; Lafont, D.; Queneau, Y.; Chambert, S.; Fitremann, J. Chem. Soc. Rev. 2007, 36,
1971–2035.
6. (a) Gagnaire, J.; Cornet, A.; Bouchu, A.; Descotes, G.; Queneau, Y. Study of
the competition between homogeneous and interfacial reactions during the synthe-
sis of surfactant sucrose hydroxyalkyl ethers in water. Colloids Surf. A 2000, 172,
125–138. (b) Queneau, Y.; Gagnaire, J.; West, J. J.; Mackenzie, G.; Goodby, J. W.
The effect of molecular shape on the liquid crystal properties of the mono-O-(2-
hydroxydodecyl)sucroses. J. Mater. Chem. 2001, 11, 2839–2844.

S. Ohkawabata et al.
672
7. Kanemaru, M.; Kuwahara, S.; Yamamoto, K.; Kadokawa, J. Self-assembly of 6-O-
and 6ꢁ-O-hexadecylsucroses mixture under aqueous conditions. Carbohydr. Res. 2010,
345, 2718–1722.
8. Otake, T. Studies of tritylated sucrose. I. Mono-O-tritylsucroses. Bull. Chem. Soc.
Jpn. 1970, 43, 3199–3205.
9. Otake, T. Studies of tritylated sucrose. II. Di-O-tritylsucroses. Bull. Chem. Soc.
Jpn. 1972, 45, 2895–2898.
10. Mach, M.; Jarosz, S.; Listkowski, A. Crown ether analogs from sucrose. J. Carbo-
hydr. Chem. 2001, 20, 485–493.
11. (a) Sofian, A. S.; Lee, C. K. Synthesis and taste properties of 4,1’,6ꢁ-trihalodeoxy
sucrose analogues. J. Carbohydr. Chem. 2001, 20, 191–205. (b) Sofian, A. S. M.; Lee,
C. K. Synthesis and taste properties of 4,1’,4’,6ꢁ-tetrahalodeoxysucrose analogues. J.
Carbohydr. Chem. 2003, 22, 185–206.
12. Kadokawa, J.; Nishikawa, T.; Sasaki, Y.; Tanaka, Y.; Kato, T.; Kaneko, Y. Synthesis
of aromatic polyamide having fluorescein moieties in the main-chain and Its conversion
into ionically cross-linked nanoparticles with Ca2+. Polym. J. 2009, 41, 893–897.